Low-dose brimonidine combinations and uses thereof

Abstract

The present invention is related to compositions containing an ophthalmological drug and low-dose brimonidine. The present invention is further related to methods of treating ophthalmological disease by administering compositions of the present invention. The present invention is further related to methods of increasing residency time of ophthalmological drugs on the surface of an eye by co-administering low-dose brimonidine.

What is claimed is: 
     
         1 . An ophthalmological composition comprising an ophthalmological drug and brimonidine at a concentration from about 0.005% to about 0.10% w/v, wherein w/v denotes weight by total volume of the composition. 
     
     
         2 . The composition of  claim 1 , wherein brimonidine is at a concentration from about 0.01% to about 0.075% w/v. 
     
     
         3 . The composition of  claim 1 , wherein brimonidine is at a concentration from about 0.06% to about 0.07% w/v. 
     
     
         4 . The composition of  claim 1 , wherein brimonidine is at a concentration from about 0.025% to about 0.045% w/v. 
     
     
         5 . The composition of  claim 1 , wherein brimonidine is at a concentration from about 0.025% to about 0.035% w/v. 
     
     
         6 . The composition of  claim 1 , wherein the ophthalmological drug is selected from the group consisting of latanoprost, bimatoprost, travaprost, tafluprost, netarsudil, carteolol, timoptic, timolol, betaloxol, levobunolol, metipranolol, brinzolamide, dorzolamide, acetazolamide, methazolamide, latanoprostene bunod, lopidine, dexmedetomidinenaphazoline, antazoline, azelastine, carbinoxamine, cyproheptadine, emedastine, hydroxyzine, levocabastine, brompheniramine, chlorpheniramine, clemastine, diphenhydramine, ketotifen, loratadine, desloratadine, cetirizine, fexofenadine, olopatadine, acrivastine, ebastine, norastemizole, levocetirizine, mizolastine, pheniramine, fluocinolone, prednisolone, dexamethasone, bethamethasone, methylprednisolone, triamcinolone, prednisolone, prednisone, hydrocortisone, cortisone, methotrexate, mycophenolate, azathioprine, cyclosporine ketorolac, aspirin, celecoxib, diflunisal, etodolac, ibuprofen, indomethacin, ketoprofen, nabumetone, naproxen, oxaprozin, salsalate, sulindac, tolmetin and pharmaceutically acceptable salts thereof and ranibizumab, bevacizumab, pazopantinib, aflibercept, adalimumab, infliximab, daclizumab, abatacept, and rituximab and combinations thereof. 
     
     
         7 . A method of treating an eye disease comprising administering a composition of  claim 1  to a subject in need thereof. 
     
     
         8 . The method of  claim 7 , wherein the eye disease is selected from the group consisting of glaucoma, allergies, macular edema, macular degeneration, diabetic retinopathy, uveitis, retinitis, choroiditis, retinopathies associated with vascular leakage and combinations thereof. 
     
     
         9 . A method of treating an eye disease comprising topically administering an ophthalmological drug concurrently or sequentially with brimonidine at a concentration from about 0.005% to about 0.1% w/v to a subject in need thereof, wherein w/v denotes weight by total volume. 
     
     
         10 . The method of  claim 9 , wherein brimonidine is at a concentration from about 0.005% to about 0.059% w/v and wherein brimonidine enhances the activity of the ophthalmological drug. 
     
     
         11 . The method of  claim 10 , wherein brimonidine is at a concentration from about 0.06% to about 0.1% w/v and wherein aqueous humor production in the eye is reduced. 
     
     
         12 . The method of  claim 10 , wherein brimonidine is formulated in a topical composition comprising brimonidine, one or more surfactants at a total concentration from about 1.0% to about 5.0% w/v and a viscosity enhancer. 
     
     
         13 . The method of  claim 12 , wherein the viscosity enhancer is selected from the group consisting of a cellulose derivative, a carbomer, a gum and a hyaluronate. 
     
     
         14 . The method of  claim 13 , wherein the viscosity enhancer is carboxymethyl cellulose at a concentration from about 0.75% to about 1.75% w/v. 
     
     
         15 . The method of  claim 9 , wherein brimonidine is at a concentration from about 0.01% to about 0.059% w/v. 
     
     
         16 . The method of  claim 9 , wherein brimonidine is at a concentration from about 0.025% to about 0.045% w/v. 
     
     
         17 . The method of  claim 9 , wherein brimonidine is at a concentration from about 0.025% to about 0.035% w/v. 
     
     
         18 . A method of increasing residency time of an ophthalmological drug on the surface of an eye comprising topically administering the ophthalmological drug concurrently or sequentially with brimonidine at a concentration from about 0.005% to about 0.059% w/v on the surface of the eye, wherein w/v denotes weight by total volume. 
     
     
         19 . The method of  claim 18 , wherein brimonidine is at a concentration from about 0.01% to about 0.059% w/v. 
     
     
         20 . The method of  claim 18 , wherein brimonidine is at a concentration from about 0.025% to about 0.045% w/v. 
     
     
         21 . The method of  claim 18 , wherein brimonidine is at a concentration from about 0.025% to about 0.035% w/v. 
     
     
         22 . An ophthalmological composition for the treatment of glaucoma comprising one or more active ingredients selected from the group consisting of netarsudil, a prostaglandin a prostaglandin analogue, a carbonic anhydrase inhibitor, a beta blocker and from about 0.005% to about 0.10% w/v brimonidine. 
     
     
         23 . The composition of  claim 22  further comprising 3.5% w/v polysorbate, 1.4% w/v carboxymethyl cellulose and wherein the one or more active ingredients are netarsudil and brimonidine. 
     
     
         24 . The composition of  claim 23 , wherein the brimonidine is at a concentration from about 0.005% to about 0.059% w/v. 
     
     
         25 . The composition of  claim 23 , wherein the brimonidine is at a concentration of about 0.065% w/v and the netarsudil is at a concentration of about 0.02% w/v. 
     
     
         26 . The composition of  claim 23 , wherein the brimonidine is at a concentration of about 0.073% w/v and the netarsudil is at a concentration of about 0.02% w/v.